We seek to characterized ERG components that originate in the proximal retina, identify their cellular origins, determine in what way they reflect retinal physiology, and test their clinical utility for evaluating human retinal diseases that are a leading cause of blindness. We recently identified a new ERG component that is elicited in a straight-forward way, using very dim stimuli in the dark-adapted state. We named the Scotopic Threshold Response (STR and have shown that it originates from the proximal retina. The STR is similar for the cat, monkey, and human, and potentially has clinical application to the physiology and pathology of the human inner retina. Preliminary studies sowed several features of the STR worth pursuing: (1) pharmacologic agents separated the STR from other ERG components and suggested an origin involving amacrine cells. (2) Although the STR is driven solely by the rod system, it followed an unexpectedly complex course of dark-adaptation and raised the possibility of correlating it with a separate scotopic pathway of cat believed to operate near absolute visual threshold. (3) Patients with normal rod b-waves can have an abnormal STR. The work will focus on correlating rod ERG components with the physiology and pharmacology of the inner retina, particularly during and after dark-adaptation. Techniques include intraretinal microelectrode studies in cat and corneal ERG recordings of monkey and human. The research aims are: (1) Correlate the purely scotopic STR and the mesopic rod-PII of the cat with activity of the rod pathway of the inner retina during the changing neural environment of dark-adaptation. (2) Use pharmacologic agents in the cat to evaluate the contributions of this pathway to the STR and to rod-PII, and to probe further the neural origin of the STR. (3) Initiate a superfused rabbit retina-eyecup preparation an characterize the peculiar "inverted-STR" of rabbit. (4) Study the STR and rod-PII in human subjects receiving pharmacological agents known or thought to affect retinal function, and correlate these with the comparable pharmacological studies of the cat and monkey ERG. (5) Test the clinical value of the STR for diagnosing human diseases that affect the inner retina, including glaucoma, diabetes, and retinal vascular occlusive disease. This work will enhance our knowledge of visual processing in the proximal retina and how this correlates with the electroretinogram. It will increase the power and scope of clinical ERG testing to probe retinal pathology in human diseases.